Breast cancer affects the lives of nearly 200,000 women every year

Breast cancer affects the lives of nearly 200,000 women every year. Progression of this disease is facilitated by the deregulation of molecular networks that create and maintain the mammary gland. Therefore, it is critical to identify these genetic networks because elucidating these pathways will identify therapeutic targets that may one day lead to better diagnostic markers, treatments, or methods to prevent this disease. In my thesis research on breast development, I have uncovered a relationship between two important signaling networks that have been viewed as independent from each other. Both of these pathways suppress branching morphogenesis, a poorly understood, but critical, process that establishes the structure of the breast. The genetic pathways that operate during normal and disease states are numerous; consequently, genomics provide a powerful approach capable of identifying signaling pathways. In this application I propose to define the components of signaling networks and their relationship to each other by employing SOLiD high throughput sequencing. The mouse mammary gland is a bi-layered, branching ductal network. It begins as a small mass of epithelial cells that differentiate, elongate and hollow to create a bilayered duct with at central lumen. This bi-layer comprises an inner layer of luminal epithelial cells that is surrounded by an outer layer of myoepithelial cells. The gland is encompassed by a basal lamina that separates it from the surrounding fat pad (Figure 1). During development, the gland undergoes repeated branching to create a tree-like structure (Silberstein, 2001.) Branching is induced by growth factors such as scatter factor (HGF) and fibroblast growth factor (FGF). In contrast, one master inhibitory regulator